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Utilize microbial elicitors of isoflavonoid production in manipulation of isoflavonoid levels. Test individual or combinations of isoflavonoid compounds induced by microbial elicitors for phytoestrogenic effects in animal systems. Test effects of phytoalexins using in vitro cell systems for PPAR transcriptional activity, adipocyte differentiation, and obesity related gene expression. Evaluate in vivo gene expression from tissue samples from ongoing experiments.
Approach:
Estrogenic and antiestrogenic activities of isoflavonoids isolated from soybean tissues/organs will be analyzed by determining their ability to support in vitro and in vivo growth of several different cancer cell lines. Compounds will be screened for estrogen activity in assays using breast cancer cells incorporating an estrogen dependent promoter coupled with a luciferase reporter gene. Compounds will be assayed in order to determine synergistic effects and to measure estrogenic potency. Also, compounds will be screened for estrogen receptor binding and breast cancer proliferation. Anitestrogenic activity will be determined for all compounds. Antiestrogenic compounds will be tested in vivo using a mouse model system with different cancer cell lines, including breast, ovarian, and prostate cells.